title: cRGD-functionalized, DOX-conjugated, and ⁶⁴Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging.
abstract: Multifunctional and water-soluble superparamagnetic iron oxide (SPIO) nanocarriers were developed for targeted drug delivery and positron emission tomography/magnetic resonance imaging (PET/MRI) dual-modality imaging of tumors with integrin α(v)β₃ expression. An anticancer drug was conjugated onto the PEGylated SPIO nanocarriers via pH-sensitive bonds. Tumor-targeting ligands, cyclo(Arg-Gly-Asp-d-Phe-Cys) (c(RGDfC)) peptides, and PET ⁶⁴Cu chelators, macrocyclic 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA), were conjugated onto the distal ends of the PEG arms. The effectiveness of the SPIO nanocarriers as an MRI contrast agent was evaluated via an in vitro r₂ MRI relaxivity measurement. cRGD-conjugated SPIO nanocarriers exhibited a higher level of cellular uptake than cRGD-free ones in vitro. Moreover, cRGD-conjugated SPIO nanocarriers showed a much higher level of tumor accumulation than cRGD-free ones according to non-invasive and quantitative PET imaging, and ex vivo biodistribution studies. Thus, these SPIO nanocarriers demonstrated promising properties for combined targeted anticancer drug delivery and PET/MRI dual-modality imaging of tumors.
authors.affiliation: Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Jamison J
authors.initials: JJ
authors.lastname: Grailer
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Rowland
authors.forename: Alireza
authors.initials: A
authors.lastname: Javadi
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Hurley
authors.forename: Yuling
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yunan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000138:chemical synthesis*; D003952:Diagnostic Imaging / Q000379:methods*; D004317:Doxorubicin / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008314:Malonates / Q000138:chemical synthesis; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D050997:Nanomedicine / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D003911:Dextrans; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; D008314:Malonates; D010456:Peptides, Cyclic; C540852:monoethyl malonate; D004317:Doxorubicin; C065507:ferumoxides